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Oligodendrocytes in a Nutshell.

Michalski JP, Kothary R - Front Cell Neurosci (2015)

Bottom Line: While the phrase is oft repeated and holds true, the last few years have borne witness to radical change in our understanding of this unique cell type.Once considered static glue, oligodendrocytes are now seen as plastic and adaptive, capable of reacting to a changing CNS.This review is intended as a primer and guide, exploring how the past 5 years have fundamentally altered our appreciation of oligodendrocyte development and CNS myelination.

View Article: PubMed Central - PubMed

Affiliation: Ottawa Hospital Research Institute , Ottawa, ON , Canada ; Department of Cellular and Molecular Medicine, University of Ottawa , Ottawa, ON , Canada.

ABSTRACT
Oligodendrocytes are the myelinating cells of the central nervous system (CNS). While the phrase is oft repeated and holds true, the last few years have borne witness to radical change in our understanding of this unique cell type. Once considered static glue, oligodendrocytes are now seen as plastic and adaptive, capable of reacting to a changing CNS. This review is intended as a primer and guide, exploring how the past 5 years have fundamentally altered our appreciation of oligodendrocyte development and CNS myelination.

No MeSH data available.


The growth-like cone and cytoskeleton in maturing oligodendrocytes. (A) Microtubules (depicted in green) run the length of OL processes in long parallel lines. F-actin (in red) is found throughout the OL, but is most heavily concentrated at the growing ends. These growing ends, or tips, are highly reminiscent of neuronal growth cones in both structure and cytoskeletal distribution. Neural cones have three distinct domains: a microtubule rich central (C) domain, an F-actin rich peripheral (P) domain, and a transient (T) domain where microtubules and F-actin overlap. We have overlaid these domains with the OL growth-cone-like structure to demonstrate similarities. In the schematic, microtubules (in green) invade the OL growth-cone centrally. Most do not advance much past this central point and are clearly delineated from the peripheral F-actin. The OL’s leading edge is replete with a meshwork of F-actin fibers (depicted in red). As well, parallel F-actin bundles (depicted as bundled long red strands), push against the membrane edge generating filopodia. A very few microtubules will penetrate the peripheral domain. In a neuronal cone, these exploratory microtubules are important for directed growth. (B) A basic schematic depicting various cytoskeletal assembly/remodeling proteins that drive or stall the oligodendrocyte’s growth cone. WAVE1 and N-WASP widen the cones lamellopodia, leading to process extension through F-actin branching and polymerization. CNP directs F-actin rearrangement, microtubule growth/bundling, as well as acts as a bridge between these two cytoskeletal components. CNP’s expression is strongly linked to OL morphogenesis; its ability to synchronize dynamic F-actin reorganization with microtubule polymerization and, therefore, process stabilization, is in large part responsible for OL outgrowth. RhoA, by contrast, acts as a stop-gate, preventing growth through generation of actomyosin contractile forces. Only when the RhoA pathway is deactivated can morphological development proceed. (C) Immunofluorescent representation of cytoskeleton and growth-like cone in the OL. The left panel depicts an immature OL with F-actin in red and α-tubulin in green. The right depicts a single growth-cone-like structure on the tip of an elongated OL process. P = peripheral, C = central, T = transient. Scale bar: 50 μm.
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Figure 3: The growth-like cone and cytoskeleton in maturing oligodendrocytes. (A) Microtubules (depicted in green) run the length of OL processes in long parallel lines. F-actin (in red) is found throughout the OL, but is most heavily concentrated at the growing ends. These growing ends, or tips, are highly reminiscent of neuronal growth cones in both structure and cytoskeletal distribution. Neural cones have three distinct domains: a microtubule rich central (C) domain, an F-actin rich peripheral (P) domain, and a transient (T) domain where microtubules and F-actin overlap. We have overlaid these domains with the OL growth-cone-like structure to demonstrate similarities. In the schematic, microtubules (in green) invade the OL growth-cone centrally. Most do not advance much past this central point and are clearly delineated from the peripheral F-actin. The OL’s leading edge is replete with a meshwork of F-actin fibers (depicted in red). As well, parallel F-actin bundles (depicted as bundled long red strands), push against the membrane edge generating filopodia. A very few microtubules will penetrate the peripheral domain. In a neuronal cone, these exploratory microtubules are important for directed growth. (B) A basic schematic depicting various cytoskeletal assembly/remodeling proteins that drive or stall the oligodendrocyte’s growth cone. WAVE1 and N-WASP widen the cones lamellopodia, leading to process extension through F-actin branching and polymerization. CNP directs F-actin rearrangement, microtubule growth/bundling, as well as acts as a bridge between these two cytoskeletal components. CNP’s expression is strongly linked to OL morphogenesis; its ability to synchronize dynamic F-actin reorganization with microtubule polymerization and, therefore, process stabilization, is in large part responsible for OL outgrowth. RhoA, by contrast, acts as a stop-gate, preventing growth through generation of actomyosin contractile forces. Only when the RhoA pathway is deactivated can morphological development proceed. (C) Immunofluorescent representation of cytoskeleton and growth-like cone in the OL. The left panel depicts an immature OL with F-actin in red and α-tubulin in green. The right depicts a single growth-cone-like structure on the tip of an elongated OL process. P = peripheral, C = central, T = transient. Scale bar: 50 μm.

Mentions: In the immature OL, F-actin is highly concentrated at the process’s leading edge. The edge is similar to that of a neuronal growth cone; it is formed of lamellipodia and filopodia, the latter extruding the surface (see Figure 3) (Rumsby et al., 2003; Fox et al., 2006). Splayed microtubules sit behind this highly active front. They invade from the more stable primary processes, themselves replete with bundled microtubules (Lunn et al., 1997; Song et al., 2001; Bauer et al., 2009). As the OL matures, and morphological complexity increases, microtubules display increasingly high levels of acetylated α-tubulin, indicating long-term stability for both microtubule and the process it inhabits (Lunn et al., 1997; Song et al., 2001; Lee et al., 2005). Taken together, cytoskeletal-mediated growth can be envisioned as follows: an F-actin rich OL “growth cone” leading the way, laying down a “track” for microtubules and the process to follow. As the cell matures, tubulin is acetylated, microtubules are stabilized, and the dense branched network is maintained (Song et al., 2001; Bauer et al., 2009).


Oligodendrocytes in a Nutshell.

Michalski JP, Kothary R - Front Cell Neurosci (2015)

The growth-like cone and cytoskeleton in maturing oligodendrocytes. (A) Microtubules (depicted in green) run the length of OL processes in long parallel lines. F-actin (in red) is found throughout the OL, but is most heavily concentrated at the growing ends. These growing ends, or tips, are highly reminiscent of neuronal growth cones in both structure and cytoskeletal distribution. Neural cones have three distinct domains: a microtubule rich central (C) domain, an F-actin rich peripheral (P) domain, and a transient (T) domain where microtubules and F-actin overlap. We have overlaid these domains with the OL growth-cone-like structure to demonstrate similarities. In the schematic, microtubules (in green) invade the OL growth-cone centrally. Most do not advance much past this central point and are clearly delineated from the peripheral F-actin. The OL’s leading edge is replete with a meshwork of F-actin fibers (depicted in red). As well, parallel F-actin bundles (depicted as bundled long red strands), push against the membrane edge generating filopodia. A very few microtubules will penetrate the peripheral domain. In a neuronal cone, these exploratory microtubules are important for directed growth. (B) A basic schematic depicting various cytoskeletal assembly/remodeling proteins that drive or stall the oligodendrocyte’s growth cone. WAVE1 and N-WASP widen the cones lamellopodia, leading to process extension through F-actin branching and polymerization. CNP directs F-actin rearrangement, microtubule growth/bundling, as well as acts as a bridge between these two cytoskeletal components. CNP’s expression is strongly linked to OL morphogenesis; its ability to synchronize dynamic F-actin reorganization with microtubule polymerization and, therefore, process stabilization, is in large part responsible for OL outgrowth. RhoA, by contrast, acts as a stop-gate, preventing growth through generation of actomyosin contractile forces. Only when the RhoA pathway is deactivated can morphological development proceed. (C) Immunofluorescent representation of cytoskeleton and growth-like cone in the OL. The left panel depicts an immature OL with F-actin in red and α-tubulin in green. The right depicts a single growth-cone-like structure on the tip of an elongated OL process. P = peripheral, C = central, T = transient. Scale bar: 50 μm.
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Figure 3: The growth-like cone and cytoskeleton in maturing oligodendrocytes. (A) Microtubules (depicted in green) run the length of OL processes in long parallel lines. F-actin (in red) is found throughout the OL, but is most heavily concentrated at the growing ends. These growing ends, or tips, are highly reminiscent of neuronal growth cones in both structure and cytoskeletal distribution. Neural cones have three distinct domains: a microtubule rich central (C) domain, an F-actin rich peripheral (P) domain, and a transient (T) domain where microtubules and F-actin overlap. We have overlaid these domains with the OL growth-cone-like structure to demonstrate similarities. In the schematic, microtubules (in green) invade the OL growth-cone centrally. Most do not advance much past this central point and are clearly delineated from the peripheral F-actin. The OL’s leading edge is replete with a meshwork of F-actin fibers (depicted in red). As well, parallel F-actin bundles (depicted as bundled long red strands), push against the membrane edge generating filopodia. A very few microtubules will penetrate the peripheral domain. In a neuronal cone, these exploratory microtubules are important for directed growth. (B) A basic schematic depicting various cytoskeletal assembly/remodeling proteins that drive or stall the oligodendrocyte’s growth cone. WAVE1 and N-WASP widen the cones lamellopodia, leading to process extension through F-actin branching and polymerization. CNP directs F-actin rearrangement, microtubule growth/bundling, as well as acts as a bridge between these two cytoskeletal components. CNP’s expression is strongly linked to OL morphogenesis; its ability to synchronize dynamic F-actin reorganization with microtubule polymerization and, therefore, process stabilization, is in large part responsible for OL outgrowth. RhoA, by contrast, acts as a stop-gate, preventing growth through generation of actomyosin contractile forces. Only when the RhoA pathway is deactivated can morphological development proceed. (C) Immunofluorescent representation of cytoskeleton and growth-like cone in the OL. The left panel depicts an immature OL with F-actin in red and α-tubulin in green. The right depicts a single growth-cone-like structure on the tip of an elongated OL process. P = peripheral, C = central, T = transient. Scale bar: 50 μm.
Mentions: In the immature OL, F-actin is highly concentrated at the process’s leading edge. The edge is similar to that of a neuronal growth cone; it is formed of lamellipodia and filopodia, the latter extruding the surface (see Figure 3) (Rumsby et al., 2003; Fox et al., 2006). Splayed microtubules sit behind this highly active front. They invade from the more stable primary processes, themselves replete with bundled microtubules (Lunn et al., 1997; Song et al., 2001; Bauer et al., 2009). As the OL matures, and morphological complexity increases, microtubules display increasingly high levels of acetylated α-tubulin, indicating long-term stability for both microtubule and the process it inhabits (Lunn et al., 1997; Song et al., 2001; Lee et al., 2005). Taken together, cytoskeletal-mediated growth can be envisioned as follows: an F-actin rich OL “growth cone” leading the way, laying down a “track” for microtubules and the process to follow. As the cell matures, tubulin is acetylated, microtubules are stabilized, and the dense branched network is maintained (Song et al., 2001; Bauer et al., 2009).

Bottom Line: While the phrase is oft repeated and holds true, the last few years have borne witness to radical change in our understanding of this unique cell type.Once considered static glue, oligodendrocytes are now seen as plastic and adaptive, capable of reacting to a changing CNS.This review is intended as a primer and guide, exploring how the past 5 years have fundamentally altered our appreciation of oligodendrocyte development and CNS myelination.

View Article: PubMed Central - PubMed

Affiliation: Ottawa Hospital Research Institute , Ottawa, ON , Canada ; Department of Cellular and Molecular Medicine, University of Ottawa , Ottawa, ON , Canada.

ABSTRACT
Oligodendrocytes are the myelinating cells of the central nervous system (CNS). While the phrase is oft repeated and holds true, the last few years have borne witness to radical change in our understanding of this unique cell type. Once considered static glue, oligodendrocytes are now seen as plastic and adaptive, capable of reacting to a changing CNS. This review is intended as a primer and guide, exploring how the past 5 years have fundamentally altered our appreciation of oligodendrocyte development and CNS myelination.

No MeSH data available.